Effect of anticardiolipin/beta2-glycoprotein I complexes on production of thromboxane A2 by platelets from patients with the antiphospholipid syndrome.
OBJECTIVE
Antiphospholipid antibodies (aPL) reactive with anionic phospholipids and beta2-glycoprotein I (beta2-GPI) are found in the sera of patients with autoimmune diseases. Clinically, aPL/beta2-GPI complexes are associated with arterial and venous thrombosis, fetal loss, and thrombocytopenia, i.e., the antiphospholipid syndrome (APS). The mechanism of thrombosis is not known. We hypothesized that aPL/beta2-GPI complexes could perturb the platelet membrane and increase production of thromboxane A2 (TXA2, a proaggregatory prostanoid).


METHODS
We isolated an IgG fraction containing anticardiolipin antibody (aCL) and the plasma cofactor, beta2-GPI, from a patient with a high titer of aCL and thrombotic cerebrovascular disease. We then examined the effect of aCL, beta2-GPI, and the aCL/beta2-GPI complex on platelet TXB2 (a stable metabolite of TXA2) biosynthesis in vitro from 7 healthy controls. We also measured in vitro platelet TXB2 biosynthesis in 7 patients with APS and in 8 controls.


RESULTS
We found: (1) significantly increased in vitro TXB2 production by platelets from controls after incubation with aCL/beta2-GPI complexes; (2) moderately increased TXB2 production by aCL alone; (3) no increase in TXB2 production by beta2-GPI alone; and (4) significantly increased 11-dehydro-TXB2, a metabolite of TXB2 production in vivo, in the urine of patients with APS compared with controls.


CONCLUSIONS
These data suggest that aCL/beta2-GPI complexes play a role in activating platelets to produce TXA2, which could contribute to the prothrombotic state found in patients with APS.
Robbins
D L
DL
Department of Internal Medicine, University of California Davis, School of Medicine, 95616, USA.
Leung
S
S
Miller-Blair
D J
DJ
Ziboh
V
V
D000328:Adult; D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000378:metabolism / Q000494:pharmacology*; D017152:Antibodies, Antiphospholipid / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D010743:Phospholipids; D053482:beta 2-Glycoprotein I; D013929:Thromboxane B2; D013928:Thromboxane A2; C049235:11-dehydro-thromboxane B2